Identification of estrogen-regulated genes in the cerebral cortex and development of a novel method to detect methylated DNA

Humphreys, Gwendolyn Isabel

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https://hdl.handle.net/2142/88248 Copy

Description

Title

Identification of estrogen-regulated genes in the cerebral cortex and development of a novel method to detect methylated DNA

Author(s)

Humphreys, Gwendolyn Isabel

Issue Date

2015-06-18

Director of Research (if dissertation) or Advisor (if thesis)

Nardulli, Ann

Doctoral Committee Chair(s)

Nardulli, Ann

Committee Member(s)

• Raetzman, Lori
• Roy, Edward J.
• Shapiro, David J.

Department of Study

Molecular & Integrative Physiology

Discipline

Molecular & Integrative Physiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Estrogen
• Ischemia
• Stroke
• Brain
• Cerebral cortex
• Gene expression

Abstract

The steroid hormone 17-β estradiol (E2) plays essential roles in diverse physiological systems including the brain. E2 regulates numerous functions in the brain including reproduction, mood, and cognition. E2 also protects the brain from a variety of in vitro and in vivo insults. In rodent studies, E2 decreases ischemic stroke damage and this protection is especially apparent in the cerebral cortex. However, the transcriptional alterations underlying E2-mediated protection in this brain region are largely unknown. To understand the role of E2 in the cerebral cortex, we examined the cerebral cortical transcriptome using a mouse model system. Adult female mice were ovariectomized and implanted with silastic tubing containing oil or E2. After 7 days, the cerebral cortices were harvested and RNA was isolated and analyzed using RNA sequencing. E2 significantly altered the expression of 88 genes in the cerebral cortex. These genes were associated with cerebrovasculature, oligodendrocytes, neurite extension, and signaling pathways. The identification of these genes provides valuable insights to better understand cortical processes that are influenced by E2 and that may be altered in menopausal women, whose E2 levels have declined. Hypoxia accompanies an ischemic event and, since E2 protects the brain from ischemic damage, we built upon our examination of E2-mediated gene expression alterations and investigated the effects of E2 on the cerebral cortical transcriptome after hypoxic exposure. E2 and hypoxia altered the expression of 1,017 genes in the cerebral cortex. These E2-regulated genes were involved in glutamatergic synapse maintenance, axon guidance, angiogenesis, cell adhesion, apoptosis, development, lipid regulation, transcriptional control, and signaling pathways. The gene expression changes in both normoxic and hypoxic conditions reveal the numerous and diverse processes that are important for understanding neuroprotection and may be helpful in developing therapeutic strategies to promote stroke recovery.

Graduation Semester

2015-8

Type of Resource

text

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http://hdl.handle.net/2142/88248

Copyright and License Information

Copyright 2015 Gwendolyn I. Humphreys

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